14-51715446-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001267046.2(FRMD6):āc.971A>Gā(p.Tyr324Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.000010 ( 0 hom. )
Consequence
FRMD6
NM_001267046.2 missense
NM_001267046.2 missense
Scores
6
9
1
Clinical Significance
Conservation
PhyloP100: 4.33
Genes affected
FRMD6 (HGNC:19839): (FERM domain containing 6) Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within apical constriction; cellular protein localization; and regulation of actin filament-based process. Predicted to be located in apical junction complex. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.88
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRMD6 | NM_001267046.2 | c.971A>G | p.Tyr324Cys | missense_variant | 10/14 | ENST00000344768.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRMD6 | ENST00000344768.10 | c.971A>G | p.Tyr324Cys | missense_variant | 10/14 | 2 | NM_001267046.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251132Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135710
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461530Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727040
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | The c.947A>G (p.Y316C) alteration is located in exon 11 (coding exon 9) of the FRMD6 gene. This alteration results from a A to G substitution at nucleotide position 947, causing the tyrosine (Y) at amino acid position 316 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MutPred
0.68
.;.;Loss of phosphorylation at Y324 (P = 0.0589);.;.;
MVP
MPC
0.59
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at